TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19259	58000;58001;58002	chr2:178595579;178595578;178595577	chr2:179460306;179460305;179460304
N2AB	17618	53077;53078;53079	chr2:178595579;178595578;178595577	chr2:179460306;179460305;179460304
N2A	16691	50296;50297;50298	chr2:178595579;178595578;178595577	chr2:179460306;179460305;179460304
N2B	10194	30805;30806;30807	chr2:178595579;178595578;178595577	chr2:179460306;179460305;179460304
Novex-1	10319	31180;31181;31182	chr2:178595579;178595578;178595577	chr2:179460306;179460305;179460304
Novex-2	10386	31381;31382;31383	chr2:178595579;178595578;178595577	chr2:179460306;179460305;179460304
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCG
• RefSeq wild type template codon: CGC
• Domain: Fn3-27
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1401
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
A/V	rs868535712	-0.349	1.0	N	0.647	0.4	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.42E-05	6.57E-05	0	0	0	None	0	0	0	0	0
A/V	rs868535712	-0.349	1.0	N	0.647	0.4	None	gnomAD-4.0.0	2.02777E-05	None	None	None	None	N	None	5.3904E-05	1.82535E-05	None	0	0	None	0	0	2.15432E-05	0	3.26691E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
A/C	0.6486	likely_pathogenic	0.6665	pathogenic	-1.033	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
A/D	0.9948	likely_pathogenic	0.9956	pathogenic	-2.726	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
A/E	0.9839	likely_pathogenic	0.9859	pathogenic	-2.453	Highly Destabilizing	1.0	D	0.788	deleterious	N	0.491536955	None	None	N
A/F	0.9613	likely_pathogenic	0.9624	pathogenic	-0.7	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
A/G	0.314	likely_benign	0.3173	benign	-1.79	Destabilizing	1.0	D	0.606	neutral	N	0.470687676	None	None	N
A/H	0.9756	likely_pathogenic	0.975	pathogenic	-2.286	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
A/I	0.9313	likely_pathogenic	0.9492	pathogenic	0.183	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/K	0.9837	likely_pathogenic	0.9851	pathogenic	-1.303	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
A/L	0.839	likely_pathogenic	0.8514	pathogenic	0.183	Stabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
A/M	0.8292	likely_pathogenic	0.8609	pathogenic	-0.122	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
A/N	0.9752	likely_pathogenic	0.9758	pathogenic	-1.823	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
A/P	0.9982	likely_pathogenic	0.9981	pathogenic	-0.263	Destabilizing	1.0	D	0.797	deleterious	N	0.49381836	None	None	N
A/Q	0.9263	likely_pathogenic	0.9243	pathogenic	-1.493	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/R	0.9435	likely_pathogenic	0.9424	pathogenic	-1.519	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
A/S	0.2486	likely_benign	0.2522	benign	-2.167	Highly Destabilizing	1.0	D	0.621	neutral	N	0.440906239	None	None	N
A/T	0.5661	likely_pathogenic	0.6059	pathogenic	-1.767	Destabilizing	1.0	D	0.71	prob.delet.	N	0.479904558	None	None	N
A/V	0.7233	likely_pathogenic	0.7768	pathogenic	-0.263	Destabilizing	1.0	D	0.647	neutral	N	0.465705897	None	None	N
A/W	0.995	likely_pathogenic	0.9946	pathogenic	-1.584	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/Y	0.9807	likely_pathogenic	0.9816	pathogenic	-1.019	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.